The eye of an animal, particularly a human, has an outer covering called a cornea, which refracts light rays as a first step in the process of the animal visualizing an object. The surface of the animal eye, particularly the human eye, is normally bathed by a tear film that is secreted by tiny glands around the eye. The tear film is primarily composed of three layers: mucous, water, and oil. The mucous layer is closest to the eye organ and serves as an anchor for the tear film to adhere to the eye. The middle layer is an aqueous layer, and the outer oil layer seals the tear film and prevents evaporation. The tear film also contains various nutritive and protective proteins and peptides. The tear film serves several purposes: it keeps the eye moist, creates a smooth surface for light to pass through the eye, nourishes the front of the eye, and provides protection from injury and infection.
The eye, particularly the cornea, can become dry, irritated, or damaged by trauma, disease, natural aging, environmental factors (such as pollutants and allergens), or by wearing contact lenses. In some cases, individuals may experience burning, a feeling of dryness, scratchiness, itchiness, or persistent irritation or inflammation. This irritation can lead to infection and/or visual impairment if not treated properly.
Red, irritated, and scratchy eyes are a common ophthalmological occurrence affecting millions of Americans each year. In some cases, individuals may experience burning, a feeling of dryness, scratchiness, itchiness, or persistent irritation or inflammation such as is often caused by particles that are lodged between the eye lid and the eye surface. This irritation can lead to infection and/or visual impairment if not treated properly.
Dry Eye.
Keratoconjunctivitis sicca (KCS), more commonly known as dry eye, affects more than 40 million Americans and countless more worldwide. KCS is an under-diagnosed disease which can produce symptoms of ocular dryness, discomfort, and in severe cases, visual impairment. KCS is the result of changes in tear film dynamics leading to one of two conditions: a decrease in aqueous tear production or an increase in tear evaporation. Both conditions create a state of hyperosmolar stress, which leads to an upregulation of several pro-inflammatory mediators and subsequent ocular surface damage. The mainstay for treatment of dry eye has been the use of over-the-counter artificial tear products. More recent advances include the additional use of topical anti-inflammatory agents to reduce inflammation and increase basal tear production.
Allergy Eye.
Allergic conjunctivitis, or allergy eye, is another fairly common ocular condition. Allergic conjunctivitis may be seasonal or perennial, and may be triggered by any number of agents. Several common treatments for allergy eye presently include antihistamines, mast cell stabilizers, nonsteroidal anti-inflammatory drugs, or corticosteroids.
Allergic conjunctivitis has an immune-mediated inflammatory component. In susceptible individuals, initial exposure to the causative allergen stimulates production of antigen-specific antibodies (such as IgE), which bind to the surface of the mast cells and basophils in the conjunctiva. Typical clinical manifestations of allergic conjunctivitis include erythema, edema, and itching. Presently, eye drops approved for the treatment of allergic conjunctivitis are aimed at preventing or treating allergic signs and symptoms. Allergy eye occurs in phases or stages, such that several hours following the initial mast cell mediated event, the clinical symptoms may worsen during the so-called late phase reaction. The late phase reaction is characterized by an influx of inflammatory cells, including neutrophils, lymphocytes, and eosinophils. This results in the release of a second wave of inflammatory mediators such as leukotrienes, prostaglandins, and platelet activating factor (PAF).
Prior Approaches.
The most common approach to treatment of irritated, allergic, and/or dry eyes has been to supplement the natural ocular tear film using so-called artificial tears instilled throughout the day. Examples of artificial tears include buffered, isotonic saline solutions, and/or aqueous solutions containing water soluble polymers that render the solutions more viscous and thus less easily shed by the eye. Tear reconstitution is also attempted by providing one or more components of the tear film such as phospholipids and oils. Phospholipid compositions have been shown to be useful in treating dry eye; see, e.g., McCulley and Shine, Tear film structure and dry eye, Contactologia, volume 20(4), pages 145-49 (1998); and Shine and McCulley, Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality, Archives of Ophth., volume 116(7), pages 849-52 (1998). Examples of phospholipid compositions for the treatment of dry eye are disclosed in U.S. Pat. No. 4,131,651 (Shah et al.), U.S. Pat. No. 4,370,325 (Packman), U.S. Pat. No. 4,409,205 (Shively), U.S. Pat. Nos. 4,744,980 and 4,883,658 (Holly), U.S. Pat. No. 4,914,088 (Glonek), U.S. Pat. No. 5,075,104 (Gressel et al.), U.S. Pat. No. 5,278,151 (Korb et al.), U.S. Pat. No. 5,294,607 (Glonek et al.), U.S. Pat. No. 5,371,108 (Korb et al.) and U.S. Pat. No. 5,578,586 (Glonek et al.).
Another approach involves the provision of lubricating substances in lieu of artificial tears. For example, U.S. Pat. No. 4,818,537 (Guo) discloses the use of a lubricating, liposome-based composition, and U.S. Pat. No. 5,800,807 (Hu et al.) discloses compositions containing glycerin and propylene glycol for treating eye irritation.
Other approaches include the use of ocular inserts that provide a tear substitute or stimulation of endogenous tear production. Such approaches have been met with limited success, and provide merely temporary and minimal symptomatic relief.
There is, however, a profound need in the art for novel safe and effective eye care treatments that allow for alleviation of eye irritation and inflammation, and/or increases wetting of the eye.